title: Novel application of polioviral capsid: development of a potent and prolonged oral calcitonin using polioviral binding ligand and Tat peptide.
abstract: BACKGROUND
  Poor absorption and proteolytic degradation are major obstacles of orally administered peptide drugs including calcitonin. Cell penetrating peptides (CPPs) and receptor binding ligands are interesting tools for the application in the delivery of these drugs.
  
  
  OBJECTIVE
  To investigate the enhancements of in vitro and in vivo salmon calcitonin (sCT) activity by Tat, a trans-activating transcriptional peptide and VP1 peptide (V) from polioviral capsid.
  
  
  METHODS
  Tat/sCT, V/sCT and V/Tat/sCT mixtures at various molar ratios were prepared and investigated for in vitro and in vivo activities of sCT.
  
  
  RESULTS
  Tat could increase in vitro sCT activity both in colon adenocarcinoma (HT-29) and mouth epidermal carcinoma (KB) cells. V/sCT (6:1) showed significant increase of intracellular calcium in HT-29 cells. V/Tat/sCT (6:1:1) gave highest increase of intracellular calcium in both cells. Oral administered Tat/sCT (1:1) showed comparable hypocalcemic effect to sCT injection with prolonged action. V/Tat/sCT (6:1:1) demonstrated hypocalcemic effect at 12 h after administration but no hypocalcemic effect was observed from V/sCT.
  
  
  CONCLUSIONS
  Positive charge from Tat might facilitate sCT uptake and absorption. Increasing of intracellular calcium in HT-29 cells by V but lacking of hypocalcemic effect from V/sCT in mice indicated the ligand-receptor mediated delivery of sCT by the interaction between V and PVR.
  
  
  CONCLUSIONS
  Potential application of V and Tat in oral calcitonin delivery system was demonstrated. Further study in a proper PVR bearing host is still needed to provide more useful information for the application of V in the development of drug delivery systems.
authors.affiliation: Faculty of Pharmacy, Chiang Mai University , Chiang Mai , Thailand .
authors.forename: Jiradej
authors.initials: J
authors.lastname: Manosroi
authors.forename: Warangkana
authors.initials: W
authors.lastname: Lohcharoenkal
authors.forename: Friedrich
authors.initials: F
authors.lastname: Götz
authors.forename: Rolf G
authors.initials: RG
authors.lastname: Werner
authors.forename: Worapaka
authors.initials: W
authors.lastname: Manosroi
authors.forename: Aranya
authors.initials: A
authors.lastname: Manosroi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002116:Calcitonin / Q000737:chemistry* / Q000378:metabolism; D002213:Capsid / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D015696:Gene Products, tat / Q000737:chemistry* / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007624:KB Cells; D008024:Ligands; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D017955:Poliovirus / Q000737:chemistry* / Q000378:metabolism; D051381:Rats
chemical_list: D015696:Gene Products, tat; D008024:Ligands; D010455:Peptides; C028815:salmon calcitonin; D002116:Calcitonin
keywords: Calcitonin; cell penetrating peptide; oral administration; peptide delivery; viral ligand